Experiments are proposed that would seek an explanation for the ability of canine distemper virus (CDV) to cause persistent infection and demyelinating sequelae in dogs. The proposed studies would make use of three strains of CDV that differ in their capacity to induce subacute encephalitis in specific-pathogen-free beagles. The studies would be undertaken with a view to developing an animal model of subacute sclerosing panencephalitis and possibly other demyelinating diseases of man. Several models of these diseases have been described; however, the canine system is unique inasmuch as neurological disease can be induced in susceptible subjects with a natural pathogen following exposure by the usual (respiratory) route of infection. We would single out for analysis, at least initially, only a few of the many factors that have been assigned a causal role in virus persistence. Prominence would be given to the use of quantitative in vitro methods and different strains of CDV to determine the part played by ts mutants, autointerference, interferon and viral glycoproteins in the persistence of virus in canine cells. Causal factors revealed in these in vitro studies would be tested for their significance in vivo by measuring the production of free infectious virus or latent virus in the lymphatic tissue and brains of dogs infected by exposure to CDV. The capacity of the three strains of CDV to provoke a cellular and humoral immune response to viral antigens would be measured. Special attention would be given to antibody specificity in this regard. In addition, we would relate viral-induced immunosuppression to the capacity of the individual virus strains to establish themselves in the host.